Predicting gene expression in the human malaria parasite Plasmodium falciparum using histone modification, nucleosome positioning, and 3D localization features.

Empirical evidence suggests that the malaria parasite Plasmodium falciparum employs a broad range of mechanisms to regulate gene transcription throughout the organism's complex life cycle. To better understand this regulatory machinery, we assembled a rich collection of genomic and epigenomic data sets, including information about transcription factor (TF) binding motifs, patterns of covalent histone modifications, nucleosome occupancy, GC content, and global 3D genome architecture. We used these data to train machine learning models to discriminate between high-expression and low-expression genes, focusing on three distinct stages of the red blood cell phase of the Plasmodium life cycle. Our results highlight the importance of histone modifications and 3D chromatin architecture in Plasmodium transcriptional regulation and suggest that AP2 transcription factors may play a limited regulatory role, perhaps operating in conjunction with epigenetic factors

Photoionization of Galactic Halo Gas by Old Supernova Remnants

We present new calculations on the contribution from cooling hot gas to the photoionization of warm ionized gas in the Galaxy. We show that hot gas in cooling supernova remnants (SNRs) is an important source of photoionization, particularly for gas in the halo. We find that in many regions at high latitude this source is adequate to account for the observed ionization so there is no need to find ways to transport stellar photons from the disk. The flux from cooling SNRs sets a floor on the ionization along any line of sight. Our model flux is also shown to be consistent with the diffuse soft X-ray background and with soft X-ray observations of external galaxies. We consider the ionization of the clouds observed towards the halo star HD 93521, for which there are no O stars close to the line of sight. We show that the observed ionization can be explained successfully by our model EUV/soft X-ray flux from cooling hot gas. In particular, we can match the H alpha intensity, the S++/S+ ratio, and the C+* column. From observations of the ratios of columns of C+* and either S+ or H0, we are able to estimate the thermal pressure in the clouds. The slow clouds require high (~10^4 cm^-3 K) thermal pressures to match the N(C+*)/N(S+) ratio. Additional heating sources are required for the slow clouds to maintain their ~7000 K temperatures at these pressures, as found by Reynolds, Hausen & Tufte (1999).Comment: AASTeX 5.01; 34 pages, 2 figures; submitted to Astrophysical Journa

Optimising TGLF for a Q=10 Burning Spherical Tokamak

TGLF transport model predictions have been assessed in the vicinity of a theoretical high β burning plasma spherical tokamak at Q=10. Linear micro-stability calculations from TGLF have been compared on a surface at mid-radius with the gyrokinetic code GS2. Differences between TGLF and GS2 spectra can be characterised by the RMS difference in growth rates, σγ. We find considerable improvement in the quality of TGLF growth rate spectrum can be achieved by increasing the number of parallel basis functions and by tuning the TGLF parameter used in the model for trapped particles, θtrap

Evolutionary History and Attenuation of Myxoma Virus on Two Continents

The attenuation of myxoma virus (MYXV) following its introduction as a biological control into the European rabbit populations of Australia and Europe is the canonical study of the evolution of virulence. However, the evolutionary genetics of this profound change in host-pathogen relationship is unknown. We describe the genome-scale evolution of MYXV covering a range of virulence grades sampled over 49 years from the parallel Australian and European epidemics, including the high-virulence progenitor strains released in the early 1950s. MYXV evolved rapidly over the sampling period, exhibiting one of the highest nucleotide substitution rates ever reported for a double-stranded DNA virus, and indicative of a relatively high mutation rate and/or a continually changing selective environment. Our comparative sequence data reveal that changes in virulence involved multiple genes, likely losses of gene function due to insertion-deletion events, and no mutations common to specific virulence grades. Hence, despite the similarity in selection pressures there are multiple genetic routes to attain either highly virulent or attenuated phenotypes in MYXV, resulting in convergence for phenotype but not genotype. © 2012 Kerr et al

CD4+T cells do not mediate within-host competition between genetically diverse malaria parasites

Ecological interactions between microparasite populations in the same host are an important source of selection on pathogen traits such as virulence and drug resistance. In the rodent malaria model Plasmodium chabaudi in laboratory mice, parasites that are more virulent can competitively suppress less virulent parasites in mixed infections. There is evidence that some of this suppression is due to immune-mediated apparent competition, where an immune response elicited by one parasite population suppress the population density of another. This raises the question whether enhanced immunity following vaccination would intensify competitive interactions, thus strengthening selection for virulence in Plasmodium populations. Using the P. chabaudi model, we studied mixed infections of virulent and avirulent genotypes in CD4+T cell-depleted mice. Enhanced efficacy of CD4+T cell-dependent responses is the aim of several candidate malaria vaccines. We hypothesized that if immune-mediated interactions were involved in competition, removal of the CD4+T cells would alleviate competitive suppression of the avirulent parasite. Instead, we found no alleviation of competition in the acute phase, and significant enhancement of competitive suppression after parasite densities had peaked. Thus, the host immune response may actually be alleviating other forms of competition, such as that over red blood cells. Our results suggest that the CD4+-dependent immune response, and mechanisms that act to enhance it such as vaccination, may not have the undesirable affect of exacerbating within-host competition and hence the strength of this source of selection for virulence

Stellar Metallicities and SNIa Rates in the Early-type Galaxy NGC5846 from ROSAT and ASCA Observations

In this paper we analyze the diffuse X-ray coronae surrounding the elliptical galaxy NGC5846, combining measurements from two observatories, ROSAT and ASCA. We map the gas temperature distribution and find a central cool region within an approximately isothermal gas halo extending to a radius of about 50 kpc, and evidence for a temperature decrease at larger radii. With a radially falling temperature profile, the total mass converges to 9.6+/-1.0 10^12 Msun at ~230 kpc radius. Using the spectroscopic measurements, we also derive radial distributions for the heavy elements silicon and iron and find that the abundances of both decrease with galaxy radius. The mass ratio of Si to Fe lies between the theoretical predictions for element production in SN Ia and SN II, suggesting an important role for SN Ia, as well as SN II, for gas enrichment in ellipticals. Using the SN Ia yield of Si, we set an upper limit of 0.012 SNU for the SN Ia rate at radii >50 kpc, which is independent of possible uncertainties in the iron L-shell modeling. We compare our observations with the theoretical predictions for the chemical evolution of ellipticals, taken from Matteucci & Gibson (1995). We conclude that the metal content in stars, if explained by the star formation duration, requires a significant decline in the duration of star formation with galaxy radius, ranging from ~1 Gyr at the center to ~0.01 Gyr at 100 kpc radius. Alternatively, the decline in metallicity with galaxy radius may be caused by a similar drop with radius in the efficiency of star formation. Based on the Si and Fe measurements presented in this paper, we conclude that the latter scenario is preferred, unless a dependence of the SN Ia rate on stellar metallicity is invoked. (Abridged).Comment: 11 pages, figures&tables included, emulapj.sty, accepted for Ap

A Local Moment Approach to magnetic impurities in gapless Fermi systems

A local moment approach is developed for the single-particle excitations of a symmetric Anderson impurity model (AIM), with a soft-gap hybridization vanishing at the Fermi level with a power law r > 0. Local moments are introduced explicitly from the outset, and a two-self-energy description is employed in which the single-particle excitations are coupled dynamically to low-energy transverse spin fluctuations. The resultant theory is applicable on all energy scales, and captures both the spin-fluctuation regime of strong coupling (large-U), as well as the weak coupling regime. While the primary emphasis is on single particle dynamics, the quantum phase transition between strong coupling (SC) and (LM) phases can also be addressed directly; for the spin-fluctuation regime in particular a number of asymptotically exact results are thereby obtained. Results for both single-particle spectra and SC/LM phase boundaries are found to agree well with recent numerical renormalization group (NRG) studies. A number of further testable predictions are made; in particular, for r < 1/2, spectra characteristic of the SC state are predicted to exhibit an r-dependent universal scaling form as the SC/LM phase boundary is approached and the Kondo scale vanishes. Results for the `normal' r = 0 AIM are moreover recovered smoothly from the limit r -> 0, where the resultant description of single-particle dynamics includes recovery of Doniach-Sunjic tails in the Kondo resonance, as well as characteristic low-energy Fermi liquid behaviour.Comment: 52 pages, 19 figures, submitted to Journal of Physics: Condensed Matte

Potential drivers of virulence evolution in aquaculture

Infectious diseases are economically detrimental to aquaculture, and with continued expansion and intensification of aquaculture, the importance of managing infectious diseases will likely increase in the future. Here, we use evolution of virulence theory, along with examples, to identify aquaculture practices that might lead to the evolution of increased pathogen virulence. We identify eight practices common in aquaculture that theory predicts may favor evolution toward higher pathogen virulence. Four are related to intensive aquaculture operations, and four others are related specifically to infectious disease control. Our intention is to make aquaculture managers aware of these risks, such that with increased vigilance, they might be able to detect and prevent the emergence and spread of increasingly troublesome pathogen strains in the future

Single-particle dynamics of the Anderson model: a local moment approach

A non-perturbative local moment approach to single-particle dynamics of the general asymmetric Anderson impurity model is developed. The approach encompasses all energy scales and interaction strengths. It captures thereby strong coupling Kondo behaviour, including the resultant universal scaling behaviour of the single-particle spectrum; as well as the mixed valent and essentially perturbative empty orbital regimes. The underlying approach is physically transparent and innately simple, and as such is capable of practical extension to lattice-based models within the framework of dynamical mean-field theory.Comment: 26 pages, 9 figure